Clinicopathologic study of deciduoid mesothelioma using SMARCB1/INI1 immunohistochemistry and fluorescence in situ hybridization

doi:10.1016/j.humpath.2019.08.016

Human Pathology

Volume 93, November 2019, Pages 23-29

https://doi.org/10.1016/j.humpath.2019.08.016 Get rights and content

Summary

Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. Malignant rhabdoid tumors, renal medullary carcinoma, and some synovial sarcomas show a loss of SMARCB1/INI1 protein, a member of the SWI/SNF chromatin-remodeling complex. All of those tumors are known to have rhabdoid cells. Some mesothelioma cases, such as those of the deciduoid type, have also been reported to possess such rhabdoid features. Since this topic has not been studied in malignant mesothelioma, we analyzed the immunohistochemical expression of SMARCB1/INI1 in malignant mesotheliomas [45 epithelioid type (including 9 deciduoid type), 12 biphasic type, and 17 sarcomatoid type]. We employed (a) SMARCB1/INI1 immunohistochemistry, using an antibody to the INI1 gene product and (b) Fisher exact test, logistic regression analysis, the Kaplan-Meier method, and the Wilcoxon test for survival analysis for prognostic factor evaluation (SAS 9.4; SAS Institute, Cary, NC). The results showed that 17 of 74 (23%) malignant mesothelioma cases (epithelioid: 24%; biphasic; 8%; sarcomatoid; 29%) had reduced SMARCB1/INI1 expression. Reduced SMARCB1/INI1 expression appeared to be more frequent in the deciduoid type (67%), of which there were admittedly only a few cases, than in either the epithelioid type (14%) or biphasic type (8%), whether or not rhabdoid cells were present, but not different between the deciduoid and sarcomatoid types. However, there was no statistically significant difference in prognosis between malignant mesotheliomas with reduced versus preserved SMARCB1/INI1 protein expression. The results suggest that in differential diagnosis, cases with reduced SMARCB1/INI1 protein expression should not be excluded from a diagnosis of malignant mesothelioma.

Introduction

Epithelioid mesothelioma can be subdivided into solid, tubulopapillary, trabecular, micropapillary, adenomatoid, clear cell, signet ring, transitional, deciduoid, small, pleomorphic, lymphohistiocytoid, and myxoid types, according to the 4th edition WHO Tumor Classification [1]. Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially reported to occur in the peritoneum of young females without a history of asbestos exposure [2], [3]. Since then, this type of mesothelioma has been reported to occur in the pleura of men and women with asbestos exposure [4]. This type of mesothelioma sometimes exhibits rhabdoid features that are characterized by discohesive cells containing abundant cytoplasm and large eccentric nuclei with prominent nucleoli [4], [5].

SMARCB1/INI1 is a member of the SWI/SNF multi-subunit chromatin-remodeling complex located on the long arm of chromosome 22 (22q11.2) [6], [7].

Malignant rhabdoid tumors, renal medullary carcinomas, epithelioid sarcomas, epithelioid malignant peripheral nerve sheath tumors, extraskeletal myxoid chondrosarcomas, and some synovial sarcomas show a loss of SMARCB1/INI1 protein expression in tumor cells, and all of these tumors are known to have rhabdoid cells [8], [9], [10], [11], [12], [13]. However, the literature contains no detailed study on this topic in malignant mesothelioma, only a single case report [14]. We analyzed the immunohistochemical expression of SMARCB1/INI1 in malignant mesotheliomas. In addition, we performed FISH analysis for homozygous and heterozygous deletion. Finally, Fisher exact test, logistic regression analysis, the Kaplan-Meier method, and the Wilcoxon test for survival analysis were employed for prognostic factor evaluation (SAS 9.4; SAS Institute, Cary, NC).

Section snippets

Patients and tissue samples

Malignant mesotheliomas [45 epithelioid type (including 9 deciduoid type), 12 biphasic type, and 17 sarcomatoid type] were collected in our laboratory at the National Defense Medical College, and at Oita Prefectural Hospital, Kochi Medical School Hospital, and Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan. Formalin-fixed paraffin-embedded neoplastic tissue blocks were available for all cases, together with clinical information. All procedures were performed with

SMARCB1/INI1 protein and BAP-1 immunoreactivity

The results of the immunohistochemical analysis are summarized in Table 1. In 17 of the 74 malignant mesotheliomas (6 cases of the deciduoid type, 5 epithelioid type, 1 biphasic type, and 5 sarcomatoid type), reduced expression of INI1 protein was recognized in all tumor cells compared to the level in positive control samples such as infiltrating lymphocytes and entrapped normal tissue (Fig. 1). Among those 17 cases, 3 cases of the epithelioid type and 2 of the deciduoid type displayed a

Discussion

Diagnosis of malignant mesothelioma is still challenging (for example, with regard to differential diagnosis of pleural mesothelioma versus lung adenocarcinoma involving the pleura, pleural mesothelioma versus squamous carcinoma of the lung involving the pleura, and pleural mesothelioma versus metastatic renal cell carcinoma), as described in the guidelines for the pathologic diagnosis of malignant mesothelioma [19]. When atypical cells are observed in the pleura or peritoneum, the first step

Acknowledgment

We thank Dr Robert Timms for correcting the English version of the manuscript.

References (35)

N.G. Ordóñez
Deciduoid mesothelioma: report of 21 cases with review of the literature
Mod Pathol
(2012)
N.G. Ordóñez
Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases
Mod Pathol
(2006)
A.N. Imbalzano et al.
Snf5 tumor suppressor couples chromatin remodeling, checkpoint control, and chromosomal stability
Cancer Cell
(2005)
J.X. Cheng et al.
Renal medullay carcinoma: rhabdoid features and the absence of INI1 expression as markers as markers of aggressive behavior
Mod Pathol
(2008)
K. Kohashi et al.
Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor
Hum Pathol
(2009)
K. Kohashi et al.
Reduced expression of SMARCB1/INI1 protein in synovial sarcoma
Mod Pathol
(2010)
A.D. Singhi et al.
The prognostic significance of BAP-1, NF2, and CDKN2A in malignant peritoneal mesothelioma
Mod Pathol
(2016)
D. Wu et al.
Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis
Am J Clin Pathol
(2013)
A. Yoshida et al.
Clinicopathological and molecular molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities
Mod Pathol
(2017)
J.L. Sauter et al.
SMARCA4-deficient thoracic sarcoma: a distinctive clinicopathological entity with undifferentiated rhabdoid morphology and aggressive behavior
Mod Pathol
(2017)

J. Wang et al.

Loss of INI1 expression in colorectal carcinoma is associated with high tumor grade, poor survival, BRAFV600E mutation, and mismatch repair deficiency

Hum Pathol

(2016)

R. Manda et al.

Absence of hSNF5/INI1 mutation in human lung cancer

Cancer Lett

(2000)

F. Galateau-Salle et al.

WHO classification of tumours of the pleura

A. Talerman et al.

Diffuse malignant peritoneal mesothelioma in a 13-year-old girl: report of a case and review of the literature

Am J Surg Pathol

(1985)

A.G. Nascimento et al.

Deciduoid peritoneal mesothelioma

An unusual phenotype affecting young females. Am J Surg Pathol

(1994)

C.W. Roberts et al.

The SW1/SNF complex-chromatin and cancer

Nat Rev Cancer

(2004)

K. Kohashi et al.

SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma

Am J Surg Pathol

(2008)

Cited by (3)

Liposarcoma of the pleural cavity
2023, Human Pathology
Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.
Malignant and borderline mesothelial tumors of the pleura
2022, Practical Pulmonary Pathology: A Diagnostic Approach
This chapter addresses the pathology of malignant and borderline mesothelial pleural neoplasms. These include mesotheliomas, both localized and diffuse types, as well as well-differentiated papillary mesothelial tumor and multicystic mesothelial tumors of borderline biological potential. Cytomorphologic features, histochemical, immunohistochemical, and molecular characteristics of these lesions are discussed, with an emphasis on the role for genomic and protein biomarkers in the diagnosis of mesothelial neoplasms and entities in the differential diagnosis.
Malignant pleural mesothelioma with heterologous elements
2022, Journal of Clinical Pathology

^☆: Competing interest: The authors declare no conflict of interest.

^☆☆: Funding/Support: This work was not supported by any organization.

^★: This work has been accepted as an abstract at the United States and Canadian Academy of Pathology 2018 annual meeting in Baltimore.

View full text

Original contributionClinicopathologic study of deciduoid mesothelioma using SMARCB1/INI1 immunohistochemistry and fluorescence in situ hybridization☆,☆☆,★

Summary

Introduction

Section snippets

Patients and tissue samples

SMARCB1/INI1 protein and BAP-1 immunoreactivity

Discussion

Acknowledgment

Mod Pathol

Mod Pathol

Cancer Cell

Mod Pathol

Hum Pathol

Mod Pathol

Mod Pathol

Am J Clin Pathol

Mod Pathol

Mod Pathol

Hum Pathol

Cancer Lett

WHO classification of tumours of the pleura

Diffuse malignant peritoneal mesothelioma in a 13-year-old girl: report of a case and review of the literature

Am J Surg Pathol

Deciduoid peritoneal mesothelioma

An unusual phenotype affecting young females. Am J Surg Pathol

The SW1/SNF complex-chromatin and cancer

Nat Rev Cancer

SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma

Am J Surg Pathol

Original contribution
Clinicopathologic study of deciduoid mesothelioma using SMARCB1/INI1 immunohistochemistry and fluorescence in situ hybridization☆,☆☆,★